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ADHD Overview and Update Rebecca Barclay, MD Child and Adolescent Psychiatrist Seattle Children’s Hospital

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Page 1: ADHD Overview and Update Rebecca Barclay, MD Child and Adolescent Psychiatrist Seattle Children’s Hospital

ADHD Overview and Update

Rebecca Barclay, MDChild and Adolescent Psychiatrist

Seattle Children’s Hospital

Page 2: ADHD Overview and Update Rebecca Barclay, MD Child and Adolescent Psychiatrist Seattle Children’s Hospital

Disclosures

• Financial: No relevant financial relationships exist.• Unlabeled/unapproved uses: Off-label medication use is

discussed in this presentation, and it will be highlighted when it occurs.

Page 3: ADHD Overview and Update Rebecca Barclay, MD Child and Adolescent Psychiatrist Seattle Children’s Hospital

ADHD—adaptive trait (but maybe not for school)

• One ADHD gene (dopamine receptor D4) allele may have conveyed advantage evolutionarily• Higher rates found in migratory populations (even today)!

Maybe this gene encouraged greater innovation/less fearfulness about the challenges of new environments.

Eisenberg DTA, Campbell B, Gray PB, Sorenson MD. Dopaminereceptor genetic polymorphisms and body composition inundernourished pastoralists: An exploration of nutrition indicesamong nomadic and recently settled Ariaal men of northernKenya. BMC Evolutionary Biology. 2008; 8(173). http://www.biomedcentral.com/1471-2148/8/173/abstract.

DEA Picture Library/De Agostini/Getty Images, http://www.npr.org/2012/09/17/161278993/what-drove-early-man-across-globe-climate-change

Page 4: ADHD Overview and Update Rebecca Barclay, MD Child and Adolescent Psychiatrist Seattle Children’s Hospital

Chris Hyde/Getty Images

Page 5: ADHD Overview and Update Rebecca Barclay, MD Child and Adolescent Psychiatrist Seattle Children’s Hospital

Source of controversy…

• In 12 months alone, NY Times search of “ADHD”:• Difficult Decisions in Treating ADHD (November 2014)• A Natural Fix for ADHD (October 2014)• Thousands of Toddlers are Medicated for ADHD (May 2014)• Reports Says Medications Use is Rising for Adults with ADHD

(May 2014)• How We Diagnose and Treat ADHD (March 2014)• Expand Pre-K, Not ADHD (February 2014)• Doctors Train to Spot Signs of ADHD (February 2014)

Page 6: ADHD Overview and Update Rebecca Barclay, MD Child and Adolescent Psychiatrist Seattle Children’s Hospital

And innovation…

• Different thinking styles may help with solving the large problems we face today.• --risk-taking and innovation when harnessed correctly could offer

valuable advantages.

Tasks of the healthcare provider…

·How do we help these children function as their brain controls mature?

· How do we help these adults avoid the dangerous pitfalls of poorly

controlled ADHD?

Page 7: ADHD Overview and Update Rebecca Barclay, MD Child and Adolescent Psychiatrist Seattle Children’s Hospital

Diagnosis

• Before 12 yo• 6 months duration• 2 or more settings• Clinically significant impairment• Not explained by other disorder• 6 symptoms of inattention or hyperactivity or both

• DSM-5 updates: 5 symptoms for adults, examples included to facilitate diagnoses across the life span, cross-situational requirement strengthened to include several symptoms in each setting, subtypes replaced with specifiers (which map to previous subtypes). http://www.dsm5.org/ProposedRevision/

Pages/proposedrevision.aspx?rid=383#. Accessed 4/25/12.

Page 8: ADHD Overview and Update Rebecca Barclay, MD Child and Adolescent Psychiatrist Seattle Children’s Hospital

Inattention

• Lacks attention to detail/careless mistakes• Difficulty sustaining attention• Does not seem to listen when spoken to• Poor follow through• Difficulty with organization• Avoids tasks requiring sustained mental effort• Loses things• Easily distracted• Forgetful

http://www.dsm5.org/ProposedRevision/Pages/proposedrevision.aspx?rid=383#. Accessed 4/25/12.

Page 9: ADHD Overview and Update Rebecca Barclay, MD Child and Adolescent Psychiatrist Seattle Children’s Hospital

Hyperactivity/Impulsivity

• Blurts out answers before question completed• Runs/climbs excessively (restless in adolescents)• Difficulty staying in seat• Difficulty engaging in quiet activities• “On the go”• Talks excessively• Interrupts• Difficulty awaiting turn• Fidgets

http://www.dsm5.org/ProposedRevision/Pages/proposedrevision.aspx?rid=383#. Accessed 4/25/12.

Page 10: ADHD Overview and Update Rebecca Barclay, MD Child and Adolescent Psychiatrist Seattle Children’s Hospital

Etiology

• Executive function deficit• Dopaminergic and noradrenergic dysregulation abnormalities

• Frontal-basal ganglia networks (inferior frontal cortex), supplementary motor area, anterior cingulate cortex, and dorsolateral prefrontal cortex, parietal, and cerebellar areas

• Heritability 76%• Causal relationship with low birth weight (even in full term infants)• Substance exposure in utero• Brain injury• Early deprivation• Preterm birth• Organophosphate pesticides

Groen-Blokhuis M et al. Evidence for a Causal Association of Low Birth Weight and Attention Problems. J. Am. Acad. Child Adolesc. Psychiatry 2011; 50(12):1247-1254. Keenan et al. Early Head Injury and Attention-Deficit/Hyperactivity Disorder. BMJ 2008; 337:a1984. Landgren et al. Prenatal Exposure and Neurodevelopmental Disorders in Children Adopted from Eastern Europe. Pediatrics 2010; May125(5):e1178-85. Bouchard M et al. Attention-deficit/hyperactivity disorder and urinary metabolites of organophosphate pesticides. Pediatrics 2010;125(6):e1270.

Page 11: ADHD Overview and Update Rebecca Barclay, MD Child and Adolescent Psychiatrist Seattle Children’s Hospital

Prevalence and Prognosis

• Prevalence 6-9% (2x boys)• Many will have symptoms persisting into adulthood.

• As many as 90% will still have some symptoms of ADHD, not necessarily meeting strict diagnostic criteria.

• Long-term consequences of ADHD: • Higher rates of traffic and other accidents, marital

difficulties, unemployment, antisocial and criminal behavior, and obesity.

• Lower household income attained• Higher rates of attempted and

completed suicide

Pliszka S. AACAP Work Group on Quality Issues. Practice Parameter. J. Am. Acad. Child Adolesc. Psychiatry 2007; 46(7):894-921.Fliers et al. ADHD Is a Risk Factor for Overweight and Obesity in Children; J Develop & Behavior Peds 2013; 34:566-574. Ljung et al. ADHD and Suicidal Behavior; JAMA Psychiatry 2014; 71(8):958-964.

Page 12: ADHD Overview and Update Rebecca Barclay, MD Child and Adolescent Psychiatrist Seattle Children’s Hospital

Comorbidities

• Language or Learning problem (25-35%)• ODD (55-85%)• Substance abuse (20-40%)• Conduct (10-20%)• Anxiety (33%)• Tic disorder (50%)• Mood disorders• Sleep problems

Pliszka S. AACAP Work Group on Quality Issues. Practice Parameter. J. Am. Acad. Child Adolesc. Psychiatry 2007; 46(7):894-921.

Page 13: ADHD Overview and Update Rebecca Barclay, MD Child and Adolescent Psychiatrist Seattle Children’s Hospital

Work-up

• In general, no testing or imaging is indicated.• Clinical diagnosis

• But some soft physical signs may be present, such as motor overflow and clumsiness.

• Rating scales can help elicit symptoms.• Comparison to peers

• Inattention/hyperactivity common in preschoolers.

• Response to stimulants is not unique to individuals with ADHD.

• Consider psychological or neuropsychological testing if low cognitive ability or achievement relative to ability.Pliszka S. AACAP Work Group on

Quality Issues. Practice Parameter. J. Am. Acad. Child Adolesc. Psychiatry 2007; 46(7):894-921.

Page 14: ADHD Overview and Update Rebecca Barclay, MD Child and Adolescent Psychiatrist Seattle Children’s Hospital

Differential Diagnosis

• Other disruptive behavior disorders• Anxiety disorders• Affective disorders• Adjustment disorders• Developmental speech and language disorders• Reactive attachment disorder• Substance abuse• Trauma

Page 15: ADHD Overview and Update Rebecca Barclay, MD Child and Adolescent Psychiatrist Seattle Children’s Hospital

Differential Diagnosis

• If other symptoms present, consider• Thyroid• Seizures• Sleep Disorder• Anemia• Sensory impairment• Brain injury• Genetic syndrome• Lead

• Medication side effects may mimic ADHD.• Bronchodilators, corticosteroids, antihistamines, antipsychotics

Page 16: ADHD Overview and Update Rebecca Barclay, MD Child and Adolescent Psychiatrist Seattle Children’s Hospital

Multimodal Treatment of Attention-Deficit/Hyperactivity Disorder Study (MTA)

• 600 children, 7-9 yo• Treatment modes:

• intensive medication management (methylphenidate tid, other drugs if necessary; algorithmic adjustments; general advice and readings);

• intensive behavioral treatment alone (parent training; structured teacher consultation; full time summer treatment program; half time classroom behavioral specialist);

• a combination of both; • routine community care (the control group).

The MTA Cooperative Group. A 14-month Randomized Clinical Trial of Treatment Strategies for Attention-Deficit/Hyperactivity Disorder. Arch Gen Psychiatry 1999; 56: 1073-1086.

Page 17: ADHD Overview and Update Rebecca Barclay, MD Child and Adolescent Psychiatrist Seattle Children’s Hospital

MTA at 14 months

• Combination treatment and medication management are superior to behavior management and community care.

• Combination treatment is better for certain areas of functioning:• oppositional/aggressive symptoms, anxiety symptoms,

reading achievement, parent-child relations, and social skills.

• 4% of patients stopped medications due to adverse effects.

The MTA Cooperative Group. A 14-month Randomized Clinical Trial of Treatment Strategies for Attention-Deficit/Hyperactivity Disorder. Arch Gen Psychiatry 1999; 56: 1073-1086.

Page 18: ADHD Overview and Update Rebecca Barclay, MD Child and Adolescent Psychiatrist Seattle Children’s Hospital

MTA at 14 months

• About 1 mg/kg optimal• Those in combination treatment ended up on lower

doses of medication than medication treatment alone group.• Medication management 32.3 mg/day • Combined care 28.7 mg/day

Greenhill et al. Impairment and Deportment Responses to Different Methylphenidate Doses in Children with ADHD: The MTA Titration Trial. J. Am. Acad. Child & Adol. Psychiatry 2001 40 (2): 180-187.

Page 19: ADHD Overview and Update Rebecca Barclay, MD Child and Adolescent Psychiatrist Seattle Children’s Hospital

MTA at 8 years

• After initial 14 months of treatment, patients returned to community care.

• No outcome differences between original treatment groups at 8 years

• Despite overall maintenance of improvement in functioning relative to pretreatment, the MTA group as a whole was functioning significantly less well than the non-ADHD classmate sample. Sustained improvement is achievable, but not normalization.

• Children with behavioral, socio-economic, or intellect advantage or best response to treatment have the best prognosis. Molina et al. The MTA at 8 Years. J. Am. Acad. Child

Adolesc. Psychiatry 2009; 48(5): 484-500.

Page 20: ADHD Overview and Update Rebecca Barclay, MD Child and Adolescent Psychiatrist Seattle Children’s Hospital

MTA at 8 years

Molina et al. The MTA at 8 Years. J. Am. Acad. Child Adolesc. Psychiatry 2009; 48(5): 484-500.

Page 21: ADHD Overview and Update Rebecca Barclay, MD Child and Adolescent Psychiatrist Seattle Children’s Hospital

Preschool ADHD Treatment Study (PATS)

• NIMH funded multi-center randomized efficacy trial• 3-5.5 yo with severe ADHD unresponsive to 10

week psychosocial intervention• 37/279 patient parents said behavioral treatment

resulted in satisfactory improvement.

Greenhill et al. Efficacy and Safety of Immediate Release Methylphenidate Treatment for Preschoolers with ADHD. J. Am. Acad. Child Adolesc. Psychiatry 2006; 45(11): 1284-1293.

Page 22: ADHD Overview and Update Rebecca Barclay, MD Child and Adolescent Psychiatrist Seattle Children’s Hospital

PATS

• Outcomes: Stimulants were effective, but• lower end doses (mean optimal methylphenidate dose 14.2 mg/day or

0.7 mg/kg)• lower effect sizes• higher rates of side effects (crabbiness, proneness to crying, irritability)

• PATS at 6 years: • Persistent ADHD diagnoses—89.9% still meeting diagnostic criteria for

ADHD. • Patients with comorbid ODD or conduct disorder had higher rates of

ADHD. • Girls experienced a steeper symptom decline (but girls’ baseline symptoms

more severe). • Hint of positive long-term benefit on parent ratings for those who

completed the study.Greenhill et al. Efficacy and Safety of Immediate Release Methylphenidate Treatment for Preschoolers with ADHD. J. Am. Acad. Child Adolesc. Psychiatry 2006; 45(11): 1284-1293. Riddle et al.

Page 23: ADHD Overview and Update Rebecca Barclay, MD Child and Adolescent Psychiatrist Seattle Children’s Hospital

PATS at 6 yrs

• PATS at 6 years: • Persistent ADHD diagnoses—89.9% still meeting

diagnostic criteria for ADHD. • Patients with comorbid ODD or conduct disorder had

higher rates of ADHD. • Girls experienced a steeper symptom decline (but girls’

baseline symptoms more severe). • Hint of positive long-term benefit on parent ratings for

those who completed the study.

Preschool ADHD (PATS) 6-Year Follow-up. J. Am. Acad. Child Adolesc. Psychiatry 2013; 52(3): 263-278.

Page 24: ADHD Overview and Update Rebecca Barclay, MD Child and Adolescent Psychiatrist Seattle Children’s Hospital

Treatment Recommendations

• Psychoeducation• Behavioral interventions

• Rewarding desirable behaviors, non-punitive consequences for negative behaviors

• Parent management training• Maintain schedule, organize home, set small goals, limit choices,

use charts/lists to maintain focus, encourage successful activities, reduce distractions, use calm discipline

• Incredible Years Parenting Program, New Forest Parenting Program, Parent-Child Interaction Therapy, Positive Parenting Program

Page 25: ADHD Overview and Update Rebecca Barclay, MD Child and Adolescent Psychiatrist Seattle Children’s Hospital

Treatment Recommendations

• Classroom interventions• Homework notebook, extended time for tasks, daily report

card, reduced distractions (seat away from window, doors), frequent breaks, physical movement when possible, tutoring, help with creating organizational system, signal from teacher when off task, occupational therapy tools.

• Classroom interventions effective in improving achievement scores, but benefits sustained only as long as interventions continued

• Training in skills deficits• Organization and planning• CBT for adolescents (builds organizational and management skill,

set up for success to avoid distractibility, adaptive thinking strategies)

Weiss, et al. A randomized controlled trial of CBT therapy for adults with ADHD with and without medication. BMC Psychiatry 2012: 12(30). Antshel, et al. Cognitive Behavioral Treatment Outcomes in Adolescent ADHD. Journal of Attention Disorders 2014: 18(6).

Page 26: ADHD Overview and Update Rebecca Barclay, MD Child and Adolescent Psychiatrist Seattle Children’s Hospital

Stimulants

• Medications for ADHD are dopaminergic or noradrenergic.

• Evidence exists for the protective effect of stimulants on comorbid disorders.• Depressive and anxiety disorders• Disruptive behavior• Family quality of life• Repeating a grade

Biederman et al. Do stimulants protect against psychiatric disorders in youth with adhd? Pediatrics. 2009 Jul:124(1): 71-8. Pliszka S. AACAP Work Group on Quality Issues. Practice Parameter. J. Am. Acad. Child Adolesc. Psychiatry 2007; 46(7):894-921.

Page 27: ADHD Overview and Update Rebecca Barclay, MD Child and Adolescent Psychiatrist Seattle Children’s Hospital

Stimulants

• Can start with either a methylphenidate or an amphetamine product • Amphetamines FDA approved > or = 3 yo• Methylphenidates FDA approved > or = 6 yo

• Similar efficacy• Side effects may be more pronounced with

amphetamine products.• Push a stimulant dose before moving on to next

trial.• Avoid unsafe doses.

Efron et al. Side effects of methylphenidate and dexamphetamine in children with attention deficit hyperactivity disorder. Pediatrics 1997; Oct 100(4): 662-6.

Page 28: ADHD Overview and Update Rebecca Barclay, MD Child and Adolescent Psychiatrist Seattle Children’s Hospital

Immediate Release Stimulants

Name Duration of Action

Methylphenidate (Ritalin, Methylin) 4-6 h

D-methylphenidate (Focalin)*2x potency of methylphenidate

4-6 h

Mixed amphetamine salts (Adderall)

4-6 h

D-amphetamine (Zenzedi, ProCentra)

4-6 h

Micromedex, accessed 5/4/12.

Page 29: ADHD Overview and Update Rebecca Barclay, MD Child and Adolescent Psychiatrist Seattle Children’s Hospital

Long Acting Stimulants

Name Mode of Delivery Duration of Action

Ritalin SR, Metadate ER, Methylin ER

Gradual release 4-8 h

Metadate CD 30% IR, 70% 3 h later 7-9 h

Ritalin LA 50% IR, 50% 4 h later 7-9 h

Quillivant XR 20% IR, 80% gradual release 8-10h

Focalin XR 50% IR, 50% 4 h later Up to 12 h

Concerta 22% IR, pump Up to 12 h

Daytrana patch Gradual release 3-5 h after removal

Adderall XR 50% IR, 50% 4 h later 8-12 h

Dexedrine spansule 50% IR, 50% gradual 10 h

Vyvanse Activated in GI tract 10 h

Micromedex, accessed 5/4/12.

Page 30: ADHD Overview and Update Rebecca Barclay, MD Child and Adolescent Psychiatrist Seattle Children’s Hospital

Side Effects

• Appetite decrease, insomnia, headaches, stomachache, dry mouth, emotional lability/aggression, priapism

• Can cause a slowing in growth velocity for weight and height

• Adrenergic effect on heart rate (5bpm in MTA)• Obtain baseline levels.• Options: decrease dose, switch, augment (for

example, add clonidine or melatonin for sleep)

Biederman J. Spencer TJ. Monuteaux MC. Faraone SV. A naturalistic 10-year prospective study of height and weight in children with attention deficit hyperactivity disorder grown up. Journal of Pediatrics 2010; 157 (4): 635-40. Pliszka S. AACAP Work Group on Quality Issues. Practice Parameter. J. Am. Acad. Child Adolesc. Psychiatry 2007; 46(7):894-921.

Page 31: ADHD Overview and Update Rebecca Barclay, MD Child and Adolescent Psychiatrist Seattle Children’s Hospital

Cardiac Concerns

• AHA says obtaining ECG reasonable.• AAP does not recommend routine ECG.

Consider ECG when on high dose, combining medications, BP/pulse change from a medication, or any cardiac symptoms.

• ADHD medications do not appear to increase the risk of serious cardiovascular events.• 1,200,438 patients with ADHD prescription matched with 2

nonusers; 2,579,104 person years: hazard ratio 0.7.

Cooper at al. ADHD Drugs and Serious Cardiovascular Events in Children and Young Adults. NEJM 2011; 365 (20): 1896-904.

Page 32: ADHD Overview and Update Rebecca Barclay, MD Child and Adolescent Psychiatrist Seattle Children’s Hospital

Cardiac Concerns

• Physical exam before initiating stimulant treatment• Ask about palpitations, syncope, chest pain,

exercise intolerance, family history of sudden death under age 35 (including drowning and motor vehicle accidents).

• Patients with known cardiac issues should be referred to cardiology before a stimulant trial.

• During treatment, monitor blood pressure and heart rate and ask about development of cardiac symptoms.

Perrin et al. Cardiovascular Monitoring and Stimulant Drugs for Attention-Deficit/Hyperactivity Disorder. Pediatrics 2008; 122(2): 451-453.

Page 33: ADHD Overview and Update Rebecca Barclay, MD Child and Adolescent Psychiatrist Seattle Children’s Hospital

ADHD and Substance Abuse

• ADHD diagnosis increases the risk of substance use and nicotine dependence.

• Early stimulant treatment may reduce or delay the onset of substance use disorder.• Recent follow up data from the MTA revealed no harm or

benefit from medication treatment in regard to rates of adolescent substance abuse.

Charach A, et al. Childhood attention-deficit/hyperactivity disorder and future substance use disorders: comparative meta-analyses. J Am Acad Child Adolesc Psychiatry 2011; 50:9–21. Wilens TE et al. Effect of prior stimulant treatment for attention-deficit/hyperactivity disorder on subsequent risk for cigarette smoking and alcohol and drug use disorders in adolescents. Arch Pediatr Adolesc Med 2008; 162:916–921; Molina Et al. Adolescent Substance Use in the Multimodal Treatment Study of Attention-Deficit/Hyperactivity Disorder. J Am Acad Child Adolesc Psychiatry 2013; 52: 251-263.

Page 34: ADHD Overview and Update Rebecca Barclay, MD Child and Adolescent Psychiatrist Seattle Children’s Hospital

ADHD and Substance Abuse

• Stimulant misuse rates of 5-9% for grade school and high school (and 5-35% in college-age individuals)

• Consider longer-acting formulations, lisdexamfetamine, and atomoxetine.

• ADHD medications used for adolescents with active substance abuse are not as effective.

Wilens TE, Adler LA, Adamson J, et al. Misuse and diversion of stimulants prescribed for ADHD: a systematic review of the literature. J Am Acad Child Adolesc Psychiatry 2008; 47:21–31.

Page 35: ADHD Overview and Update Rebecca Barclay, MD Child and Adolescent Psychiatrist Seattle Children’s Hospital

Tics and ADHD

• High comorbidity• Multi-site international database of 3500 tic disorder

patients: 60% also have ADHD

• Stimulants and Tics• “Although stimulants have not been shown to worsen tics

in most people with tic disorders, they may nonetheless exacerbate tics in individual cases. In these instances, treatment with alpha agonists or atomoxetine may be an alternative.” --Cochrane Review, 2011

Freeman RD, Fast DK, Burd L, Kerbeshian J, Robertson MM, Sandor P. An international perspective on Tourette syndrome: selected findings from 3500 individuals in 22 countries. Developmental Medicine and Child Neurology 2000; 42(7): 436-47. Pringsheim T. Steeves T. Pharmacologic Treatment for ADHD in Children with Comorbid Tic Disorders. Cochrane Database of Systemic Reviews 2011: (4):CD007990.

Page 36: ADHD Overview and Update Rebecca Barclay, MD Child and Adolescent Psychiatrist Seattle Children’s Hospital

ADHD and Irritability

• Recent publication from the MTA examined irritability (not headstrong oppositional behavior) and treatment outcomes.• Irritability contributed to impairment and showed longitudinal

continuity.

Intervention Effect Size

Combined treatment 0.82

Medication management 0.63

Community comparison 0.48

Behavioral treatment 0.42

Fernandez de la Cruz, et al. Treatment of Children with ADHD: Results from the MTA. Journal of the American Academy of Child & Adolescent Psychiatry 2015;54(1):62-70.

Page 37: ADHD Overview and Update Rebecca Barclay, MD Child and Adolescent Psychiatrist Seattle Children’s Hospital

Treatment Hierarchy

• If stimulants are ineffective, revisit diagnosis.

• Use a single medication when possible.

Page 38: ADHD Overview and Update Rebecca Barclay, MD Child and Adolescent Psychiatrist Seattle Children’s Hospital

Atomoxetine

• Brand name: Strattera• Noradrenergic reuptake inhibitor• Once daily or twice daily dosing• Start at 0.5 mg/kg/day for 2 weeks. Increase to 1.2

mg/kg/day.• Maximum 100 mg or 1.4 mg/kg (whichever is less).• Metabolized by P450 2D6 pathway• Approved > or = 6 yo

Pliszka S. AACAP Work Group on Quality Issues. Practice Parameter. J. Am. Acad. Child Adolesc. Psychiatry 2007; 46(7):894-921.

Page 39: ADHD Overview and Update Rebecca Barclay, MD Child and Adolescent Psychiatrist Seattle Children’s Hospital

Atomoxetine

• Can be helpful to anxiety

• Can take up to 6 weeks for benefit• Counsel family on delayed effect compared to stimulants.

• Effect size 0.6 (similar to guanfacine) • For comparison, effect size of stimulants approximately 0.9• For reference, effect size 0.2 is mild, 0.6 is moderate, and

0.8 is high.

Pliszka S. AACAP Work Group on Quality Issues. Practice Parameter. J. Am. Acad. Child Adolesc. Psychiatry 2007; 46(7):894-921.

Page 40: ADHD Overview and Update Rebecca Barclay, MD Child and Adolescent Psychiatrist Seattle Children’s Hospital

Atomoxetine Response

Newcorn et al. Clinical Responses to Atomoxetine in Attention-Deficit/Hyperactivity Disorder. J. Am. Acad. Child Adolesc. Psychiatry 2009; 48 (5): 511-518.

Page 41: ADHD Overview and Update Rebecca Barclay, MD Child and Adolescent Psychiatrist Seattle Children’s Hospital

Atomoxetine side effects

• GI distress, sedation (insomnia in adults)• Possible suppression in growth velocity• Not recommended if structural cardiac

abnormalities, cardiomyopathy, or rhythm abnormalities

• Warning for liver disease (2 reports; none in 6000 patients in clinical trial)• Monitoring of LFTs not recommended.

• Boxed warning for suicidal thinking (risk of 4/1000 in a large controlled study); no completed suicides

Micromedex, accessed 5/4/12.

Page 42: ADHD Overview and Update Rebecca Barclay, MD Child and Adolescent Psychiatrist Seattle Children’s Hospital

Alpha agonists

• May be more effective for hyperactivity than inattention

• Clonidine more soporific; guanfacine may be better for inattention

• Soporific effect may wane after 2-3 weeks• May not see full benefit for 4-6 weeks• Sedation, dizziness, hypotension, bradycardia• Review personal and family cardiac history• Review risk of rebound hypertension

Page 43: ADHD Overview and Update Rebecca Barclay, MD Child and Adolescent Psychiatrist Seattle Children’s Hospital

Guanfacine

Starting dose Maximum dose

Half life

FDA

Guanfacine <45kg, 0.5 mg qhs;>45 kg, 1 mg qhs

2 mg (27-40 kg); 3 mg (40-45 kg); 4 mg (>45 kg)

14 h Not approved

Guanfacine extended release (Intuniv)

1 mg daily 4 mg 16 h Approved 6-17yo

Pliszka S. AACAP Work Group on Quality Issues. Practice Parameter. J. Am. Acad. Child Adolesc. Psychiatry 2007; 46(7):894-921.

Wait one week between dose increases.

Page 44: ADHD Overview and Update Rebecca Barclay, MD Child and Adolescent Psychiatrist Seattle Children’s Hospital

Clonidine

Starting dose Maximum dose

Half life

FDA

Clonidine <45kg, 0.05 mg qhs>45 kg, 0.1 mg qhs

0.2 mg (27-40 kg); 0.3 mg (40-45 kg); 0.4 mg (>45 kg).

12 h Not approved

Clonidine extended release (Kapvay)

0.1 mg qhs; doses greater than 0.1 mg should be bid

0.4 mg 12-16 h

Approved 6-17yo

Pliszka S. AACAP Work Group on Quality Issues. Practice Parameter. J. Am. Acad. Child Adolesc. Psychiatry 2007; 46(7):894-921.

Wait one week between dose increases.

Page 45: ADHD Overview and Update Rebecca Barclay, MD Child and Adolescent Psychiatrist Seattle Children’s Hospital

Clonidine

http://www.kapvay.com/Kapvay_final_09.28.10.pdf. Prescribing information.

Page 46: ADHD Overview and Update Rebecca Barclay, MD Child and Adolescent Psychiatrist Seattle Children’s Hospital

Clonidine

• Sudden death in four youths receiving clonidine and methylphenidate.• No causality established. No other cases identified.• Reduce MPH dose by 40% when combined with clonidine.

Consider ECG.

• High profile case of death of 4 yo girl in Massachusetts on clonidine. Parents administered doses above prescribed; convicted of murder.• Advise families about importance of following dosing instructions

exactly. • Consider care-giving environment of child. • Monitor frequency of refills.

Pliszka S. AACAP Work Group on Quality Issues. Practice Parameter. J. Am. Acad. Child Adolesc. Psychiatry 2007; 46(7):894-921.Lexicomp Inc. Guanfacine: Pediatric Drug Information. 2012. Accessed 8/13/12.

Page 47: ADHD Overview and Update Rebecca Barclay, MD Child and Adolescent Psychiatrist Seattle Children’s Hospital

Bupropion

• Brand name: Wellbutrin

• Not FDA approved for pediatric use• Combined dopaminergic/noradrenergic mechanism of

action• Consider when primary treatments have failed or in

patients with co-occurring mood disorders, substance abuse, or smoking.

Micromedex, accessed 5/4/12.

Page 48: ADHD Overview and Update Rebecca Barclay, MD Child and Adolescent Psychiatrist Seattle Children’s Hospital

Bupropion

• Side effects: insomnia, appetite decrease, less commonly tics, seizures

• Risk of drug induced seizures increases 10x at doses > 450 mg/day

• Starting dose less than 150 mg/day or 3mg/kg/day• Maximum dose less than 300 mg/day or 6

mg/kg/day• No single dose greater than 150 mg

Kratochvil CJ, Daughton JM. Review of ADHD Pharmacotherapies: Advantages, Disadvantages, and Clinical Pearls. J. Am. Acad. Child Adolesc. Psychiatry 2009; 48: 240-248.

Page 49: ADHD Overview and Update Rebecca Barclay, MD Child and Adolescent Psychiatrist Seattle Children’s Hospital

Omega 3

• Not FDA approved.• Meta-analysis 699 patients--small but significant effect

(effect size 0.31)• Additional recent meta-analyses also supports benefit• Can be used to augment traditional pharmacologic

interventions or for families that decline other pharmacologic options

• Look for EPA doses between 450 mg and 600 mg

Bloch M, Qawasami A. Omega-3 Fatty Acid Supplementation for the Treatment of Children With Attention-Deficit/Hyperactivity Disorder Symptomatology: Systematic Review and Meta-Analysis. J. Am. Acad. Child and Adolesc. Psychiatry 2011; 50: 991-1000.Sonuga-Barke et al. Nonpharmacological Interventions for ADHD: Systematic Review and Meta-Analyses of Randomized Controlled Trials of Dietary and Psychological Treatments. Am J Psychiatry 2013:170(3)p;275-289.

Page 50: ADHD Overview and Update Rebecca Barclay, MD Child and Adolescent Psychiatrist Seattle Children’s Hospital

Dietary intervention

• Recent meta-analysis showed some mild benefit from elimination of food color from diet. • But effects may be limited to those with suspected food

sensitivities.• Elimination diet did not demonstrate significant benefit.

Sonuga-Barke et al. Nonpharmacological Interventions for ADHD: Systematic Review and Meta-Analyses of Randomized Controlled Trials of Dietary and Psychological Treatments. Am J Psychiatry 2013:170(3); 275-289.

Page 51: ADHD Overview and Update Rebecca Barclay, MD Child and Adolescent Psychiatrist Seattle Children’s Hospital

Neurofeedback

• ADHD: increased theta activity (4-8 Hz) and reduced beta activity (>13 Hz) compared to non-affected peers

• Neurofeedback computer program provides immediate feedback based on EEG activity, and children learn to induce the desired brain activity.

• Review of 15 studies (only 4 randomized) including 1100 children shows benefits to impulsivity and inattention.

• Other recent high quality meta-analyses notes additional blinded assessments needed before neurofeedback can be supported as a treatment for ADHD.

Arns et al. Efficacy of Neurofeedback Treatment in ADHD. Clinical EEG and Neuroscience 2009; 40 (3): 180-189. Sonuga-Barke et al. Nonpharmacological Interventions for ADHD: Systematic Review and Meta-Analyses of Randomized Controlled Trials of Dietary and Psychological Treatments. Am J Psychiatry 2013:170(3); 275-289.

Page 52: ADHD Overview and Update Rebecca Barclay, MD Child and Adolescent Psychiatrist Seattle Children’s Hospital

Computer training

• Small studies thus far • Some indication of improvement, often targeting existing

specific neuropsychological deficits (working memory)• Improvement on student self-rating, parent and teacher

ratings not consistent• School-based interventions promising concept• Need additional larger studies

Amonn, et al. Evaluation of computer-based neuropsychological training in children with ADHD. NeuroRehabilitation 2013:32(3). Klingberg T, et al. Computer training of working memory in children with ADHD—a randomized controlled trial 2005:44(2). Steiner N, et al. Computer-based attention training in the schools for children with ADHD: a preliminary trial. Clinical Pediatrics 2011:50(7). Rabiner DL, et al. A randomized trial of two promising computer-based interventions for students with attention difficulties. J Abnorm Child Psychol 2010: 38(1).

Page 53: ADHD Overview and Update Rebecca Barclay, MD Child and Adolescent Psychiatrist Seattle Children’s Hospital

Physical Exercise

• Recent review (16 studies combined) indicates exercise may improve executive functioning and behavioral symptoms associated with ADHD.• May enhance neural growth and alter gene expression• Effect size varied from small to large. Further investigation

needed. Concluding causality problematic.

Rommel et al. Protection from Genetic Diathesis in ADHD. JAACAP 2013; 52(9): 900-910.

Page 54: ADHD Overview and Update Rebecca Barclay, MD Child and Adolescent Psychiatrist Seattle Children’s Hospital

Management Wrap up

• Make only 1 change at a time to correctly attribute benefit and side effects.

• Assess after 1 year whether on-going treatment is needed.

Page 55: ADHD Overview and Update Rebecca Barclay, MD Child and Adolescent Psychiatrist Seattle Children’s Hospital

Questions? Call PAL.

Page 56: ADHD Overview and Update Rebecca Barclay, MD Child and Adolescent Psychiatrist Seattle Children’s Hospital

Case

• 8 yo boy (25 kg) presents with mother requesting evaluation and treatment. His behavioral problems began to be noticed in preschool when teachers commented that he was hyperactive, aggressive, and did not listen. Current issues include that he is still restless, on the go, into everything, bothers the family dog, needs frequent redirection, messy, forgetful, and irritable with redirection at times. He is academically falling behind.

Page 57: ADHD Overview and Update Rebecca Barclay, MD Child and Adolescent Psychiatrist Seattle Children’s Hospital

C a s e

• Normal pregnancy and infancy. Medically well. Family history significant for ADHD in an older sister and an aunt with bipolar. The family recently moved to join your practice from out of state because the parents are divorcing. The patient becomes tearful in the office when talking about missing his father. A trial of MPH 10 mg daily ineffective just before moving out of previous state. Now he is off all medications. You note hyperactivity on exam.

Page 58: ADHD Overview and Update Rebecca Barclay, MD Child and Adolescent Psychiatrist Seattle Children’s Hospital

C a s e

• Vanderbilt supports ADHD at school and home. Teachers note he is a happy and well-adjusted kid despite ADHD symptoms. SMFQ negative. Additional inquiry with patient and mother indicate he still enjoys activities he used to enjoy, has good energy level, is hopeful, and can be joyful.

Page 59: ADHD Overview and Update Rebecca Barclay, MD Child and Adolescent Psychiatrist Seattle Children’s Hospital

C a s e

• Adderall XR trial partially effective to 15 mg but becomes irritable.

• Next a Focalin XR trial is pursued. He tolerates 10 mg well with no side effects and partial treatment.

• He responds nicely to 15 mg dose with only one side effect of mild difficulty with sleep initiation.

Page 60: ADHD Overview and Update Rebecca Barclay, MD Child and Adolescent Psychiatrist Seattle Children’s Hospital

Case

• He responded well to melatonin 3 mg at hs. Grades are improving. He’s happier and engaged in therapy. Psychologic testing report notes ADHD symptoms during testing and identifies a math learning disorder as well for which he gets additional support at school. Family is pleased with his progress.

Page 61: ADHD Overview and Update Rebecca Barclay, MD Child and Adolescent Psychiatrist Seattle Children’s Hospital
Page 62: ADHD Overview and Update Rebecca Barclay, MD Child and Adolescent Psychiatrist Seattle Children’s Hospital

Case 2

• 3 yo girl with daycare behavioral problems, including hitting and biting. Mom says patient has been asked not to return to daycare. Aggression often happens when patient wants something or is frustrated. You notice it’s difficult to understand her speech, but parents understand everything.

Page 63: ADHD Overview and Update Rebecca Barclay, MD Child and Adolescent Psychiatrist Seattle Children’s Hospital

Case 2

• She is very active and difficult to contain.• There is an older brother with ADHD who improved with

methylphenidate.• Father lost his job 5 months ago and is looking for work.

The parents have a history of conflict with each other.

Page 64: ADHD Overview and Update Rebecca Barclay, MD Child and Adolescent Psychiatrist Seattle Children’s Hospital

Case 3

• 9 year old who parents report is defiant, refuses requests, does not respect family rules (stays out playing with neighborhood friends longer than allowed), and fights with sister. He is very bright, but grades are variable. Parents feel he mentally checks out.

Page 65: ADHD Overview and Update Rebecca Barclay, MD Child and Adolescent Psychiatrist Seattle Children’s Hospital
Page 66: ADHD Overview and Update Rebecca Barclay, MD Child and Adolescent Psychiatrist Seattle Children’s Hospital

Case 3

• Patient says parents favor his sister and the rules at home are unfair. He sees no problems with himself at all.

• You feel he is likeable, well-spoken, engages appropriately, and is self-assured.

• Parents are angry. They want a medication to fix this. Mom shares that bio father was manipulative and verbally abusive with a history of legal difficulties for drugs and violent behavior.

Page 67: ADHD Overview and Update Rebecca Barclay, MD Child and Adolescent Psychiatrist Seattle Children’s Hospital

Case 3

• Referred for counseling and behavior management training. Therapist reports Mom saw patient as turning into bio Dad. Therapist coached a different view of patient, encouraged positive time, and consistent limits (they had been favoring other sib).

• Defiance improved.